High fat diet may cause changes in the brain: study

October 24, 2016

Washington, Oct 24: In a recent study, scientists have discovered a new mechanism that regulates obesity. The study shows that this new mechanism can potentially be targeted to treat obesity.

highfatSenior author of the study Makoto Fukuda said, "It's well known that the brain is involved in the development of obesity, but how a high-fat diet changes the brain so it triggers the accumulation of body fat is still unclear."

The team studied the mouse Rap1 gene, which is expressed in a variety of tissues, including the brain where it is involved in functions such as memory and learning. Little was known, however, of the role brain Rap1 plays in energy balance.

To explore the role Rap1 plays in a mouse model, the scientists selectively deleted the Rap1 gene in a group of neurons in the hypothalamus, a region of the brain that is involved in regulating whole-body metabolism.

The scientists had two groups of mice. In one group, the mice were genetically engineered to lack the Rap1 gene, while the control group had a functional Rap 1 gene. Then, the scientists fed the mice in both groups a high-fat diet in which 60 percent of the calories came from fat.

As expected, the control mice with a working Rap1 gene gained weight, but, in comparison, the mice that lacked Rap 1 had markedly reduced body weight and less body fat. Interestingly, when both groups of mice were fed a normal diet, both showed similar weights and body fat.

The scientists then looked closer at why the mice lacking the Rap1 gene had not gained weight despite eating a high-fat diet.

"We observed that the mice lacking Rap1 were not more physically active. However, they ate less and burned more body fat than mice with Rap1," said Fukuda.

Adding, "These observations were associated with the hypothalamus producing more of a hormone that reduces appetite, called POMC, and less of hormones that stimulate appetite, called NPY and AgRP." These mice also had lower levels of blood glucose and insulin than controls.

The scientists also were interested in studying whether leptin changed in mice lacking Rap1.

Leptin, the 'satiety hormone' produced by fatty tissue, helps regulate body weight by inhibiting appetite. Obese people, however, do not respond to leptin's signals of satiety, and the blood levels of leptin are higher than those in non-obese people. Leptin resistance is a hallmark of human obesity.

Mice that lacked Rap1 and ate a high-fat diet, on the other hand, did not develop leptin resistance; they were able to respond to leptin and this was reflected in the hormone's lower blood levels.

The team also tested the effect of inhibiting Rap1 with drugs instead of deleting the gene on mice on a high-fat diet. The scientists inhibited RAP1 action with inhibitor ESI-05.

"When we administered ESI-05 to obese mice, we restored their sensitivity to leptin to a level similar to that in mice eating a normal diet. The mice ate less and lost weight," he said.

The scientists have shown a new mechanism by which the brain can affect the development of obesity triggered by consuming a high-fat diet.

Consuming a high-fat diet results in changes in the brain that increase Rap1 activity, which in turn leads to a decreased sensitivity to leptin, and this sets the body on a path to obesity.

"This new mechanism involving Rap1 in the brain may represent a potential therapeutic target for treating human obesity in the future," said Fukuda.

The study appeared in Cell Reports today.

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News Network
February 4,2020

Boston, Feb 4: Practising yoga may increase levels of a messenger molecule involved in regulating brain activity, and completing one yoga class per week may maintain elevated levels of this chemical, according to a study which may lead to better ways of mitigating depressive symptoms.

The study, published in the Journal of Alternative and Complementary Medicine, assessed a group of 30 clinically depressed patients who were randomly divided into two groups.

According to the researchers, including those from Boston University in the US, both groups engaged in coherent breathing, and Iyengar yoga -- a form of hatha yoga, developed by B. K. S. Iyengar, emphasising on detail, precision, and alignment in the performance of yoga postures.

The only difference between the groups, the scientists said, was the number of 90 minute yoga sessions, and home sessions in which each group participated.

Over three months, they said, the high-dose group (HDG) was assigned three sessions per week, while the low-intensity group (LIG) engaged in two sessions per week.

The participants underwent magnetic resonance imaging (MRI) scans of their brain before the first and after the last yoga session, and also completed a clinical depression scale to monitor their symptoms, the study noted.

Results of the study revealed that both groups had improvement in depressive symptoms after three months.

Their MRI analysis showed that levels of the brain messenger molecule GABA were elevated after three months of yoga, as compared to the levels before starting yoga.

According to the study, this increase was found for approximately four days after the last yoga session, but the rise was no longer observed after about eight days.

"The study suggests that the associated increase in GABA levels after a yoga session are 'time-limited' similar to that of pharmacologic treatments such that completing one session of yoga per week may maintain elevated levels of GABA," explained study co-author Chris Streeter from Boston University.

Providing evidence-based data may help in getting more individuals to try yoga as a strategy for improving their health and well-being, the scientists said.

"A unique strength of this study is that pairing the yoga intervention with brain imaging provides important neurobiological insight as to the 'how' yoga may help to alleviate depression and anxiety," said study co-author Marisa Silveri from Harvard University.

In this study, we found that an important neurochemical, GABA, which is related to mood, anxiety, and sleep, is significantly increased in association with a yoga intervention," Silveri said.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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Agencies
June 10,2020

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.

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